Date: 2013-02-26
Type of information:
phase: 3
Announcement: update
Company: Antisense Pharma, now Isarna Therapeutics(Germany)
Product: trabedersen
Action mechanism: AP 12009 is a phosphorothioate antisense oligodeoxynucleotide specific for the mRNA of human Transforming Growth Factor beta 2 (TGF-beta-2), which is applied intratumorally. This gene-silencing substance inhibits this growth factor at its translational level.
Disease: high-grade brain tumors (recurrent or refractory anaplastic astrocytoma or secondary glioblastoma)
Therapeutic area: Cancer - Oncology
Country: USA, argentina, Austria, Brazil, Canada, France, Germany, Hungary, India, Mexico, Poland, Russia, South Korea, Spain,Taiwan, UK
Trial
details: The purpose of the Phase III study SAPPHIRE is to compare the safety and efficacy of the 10 µM concentration of AP 12009 (trabedersen) and standard chemotherapy (temozolomide, BCNU, CCNU) in adult patients with recurrent or refractory anaplastic astrocytoma (AA, WHO grade III) or secondary glioblastoma (GBM, WHO grade IV). (NCT00761280)
Latest
news: * On February 26, 2013, Antisense Pharma has announced a revised development path for trabedersen
The data analysis of “SAPPHIRE” (G005), trabedersen’s early terminated phase III study in glioma, is in progress. Due to a need for additional outcome data collection, final results are now expected within the third quarter of 2013. However, preliminary safety data analyses revealed that the benefit/risk ratio might not be in favor of the trabedersen treatment arm due to serious adverse events (SAE) associated with the local mode of administration of the drug in this trial. The convention-enhanced delivery (CED) of trabedersen via intra-cranial infusion with surgical catheter placement seemed to result in a distinct, clinically relevant imbalance of SAEs observed. In light of this finding, the company decided that the risk to the patient outweighs the potential clinical benefits for this type of administration of the drug. As a consequence, the company will no longer pursue further development of the local administration of trabedersen in glioma.
Future clinical development of TGF-Beta targeted drugs in glioma is still considered for the ‘Next Generation’ TGF-Beta oligonucleotide development program based on the encouraging survival data for anaplastic astrocytoma from an earlier glioma trial with trabedersen (G004). From now onwards, trabedersen’s development path will only focus on the systemic intravenous (IV) mode of administration.
This decision is further supported by the findings from the Phase I/II clinical study (P001) presented at ASCO in June 20122 The data demonstrated that the systemic IV administration of trabedersen treatment is safe and well tolerated by patients. First clinical signs of efficacy were observed in this study with encouraging survival outcomes for patients suffering from pancreatic cancer or malignant melanoma when compared to historical controls. With this intent, Antisense Pharma is currently under way to launch a clinical Phase II study to evaluate systemic, intravenous trabedersen treatment in patients suffering from malignant melanoma, pancreatic cancer and other tumors by the second half of 2013. This clinical trial will be conducted in two stages. The first stage has a dose-confirmatory component and will further define the pharmacodynamic (PD) activity of trabedersen in terms of TGF-Beta2 target down-regulation as a primary PD parameter and immunomodulation in the selected patient populations. Upon successful completion of the first stage, the second stage of the study is set to demonstrate a survival benefit over standard chemotherapy for one or two key tumor indications in a larger patient population.
* On February 2, 2011, the South Korean health agency KFDA as well as the Taiwanese health agency TFDA have granted their approvals for the implementation of clinical studies using the anti-cancer drug trabedersen for patients with high-grade brain tumors.
With this approval, the Southeast Asian health agencies KFDA and TFDA have paved the way for the implementation of the pivotal Phase III study SAPPHIRE with the TGF-ß2 inhibitor trabedersen.
The substance is currently also in clinical development for indications such as advanced pancreas carcinoma, malignant melanoma and colorectal carcinoma. The involvement of Southeast Asian countries for clinical testing of trabedersen is part of Antisense Pharma’s strategic development program for the global marketing of this compound. Including South Korea and Taiwan, a total of 13 countries are now participating in the international pivotal study.The randomized and actively controlled Phase III study SAPPHIRE is scheduled to begin at selected medical centers in South Korea and Taiwan during the first quarter of 2011.
